Method based on GC–MS to study the influence of tricarboxylic acid cycle metabolites on cardiovascular risk factors

Calderón-Santiago, M.; Priego-Capote, Feliciano; Galache-Osuna, J.G.; Castro, M.D. Luque de

doi:10.1016/j.jpba.2012.10.029

Cited by 29 publications

(20 citation statements)

References 28 publications

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“…Previous methods have used N , O -bis-(trimethylsilyl)acetamide (BSA) [32], N -trimethylsilyl- N -methyl trifluoroacetamide (MSTFA) [33], BSTFA and trimethylchlorosilane (TMCS) [34], tributylamine [35], derivatizing reagents with a longer analysis time [35] and lower sensitivity [34] for selected energy metabolites [33,36] analyzed by GCMS [34,36] and LCMS [33,35] (S1 Table). A major lacuna in even the most recently published methods is metabolite coverage.…”

Section: Resultsmentioning

confidence: 99%

Metabolic profiling by gas chromatography-mass spectrometry of energy metabolism in high-fat diet-fed obese mice

et al. 2017

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A novel, selective and sensitive single-ion monitoring (SIM) gas chromatography-mass spectrometry (GCMS) method was developed and validated for the determination of energy metabolites related to glycolysis, the tricarboxylic acid (TCA) cycle, glutaminolysis, and fatty acid β-oxidation. This assay used N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA) containing 1% tert-butyldimethylchlorosilane (TBDMCS) as derivatizing reagent and was highly reproducible, sensitive, specific and robust. The assay was used to analyze liver tissue and serum from C57BL/6N obese mice fed a high-fat diet (HFD) and C57BL/6N mice fed normal chow for 8 weeks. HFD-fed mice serum displayed statistically significantly reduced concentrations of pyruvate, citrate, succinate, fumarate, and 2-oxoglutarate, with an elevated concentration of pantothenic acid. In liver tissue, HFD-fed mice exhibited depressed levels of glycolysis end-products pyruvate and lactate, glutamate, and the TCA cycle intermediates citrate, succinate, fumarate, malate, and oxaloacetate. Pantothenate levels were 3-fold elevated accompanied by a modest increased gene expression of Scl5a6 that encodes the pantothenate transporter SLC5A6. Since both glucose and fatty acids inhibit coenzyme A synthesis from pantothenate, it was concluded that these data were consistent with downregulated fatty acid β-oxidation, glutaminolysis, glycolysis, and TCA cycle activity, due to impaired anaplerosis. The novel SIM GCMS assay provided new insights into metabolic effects of HFD in mice.

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Section: Resultsmentioning

confidence: 99%

Metabolic profiling by gas chromatography-mass spectrometry of energy metabolism in high-fat diet-fed obese mice

et al. 2017

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“…Apparently, the consumption of onion enhanced the modification of metabolites incited by the HC diet. However, TCA impairments have been correlated with multiple diseases where oxidative stress plays a key role, and it has been suggested that an ineffective TCA cycle might be an adaptive response directed at diminishing reactive oxygen species (ROS) production and extend cellular longevity [37,38]. Thereby, the effect of the onion ingredient in this metabolic knot should be carefully examined and needs further study.…”

Section: Resultsmentioning

confidence: 99%

Metabolomic Fingerprinting in the Comprehensive Study of Liver Changes Associated with Onion Supplementation in Hypercholesterolemic Wistar Rats

González-Peña

Dudzik

Garcı́a

et al. 2017

IJMS

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The consumption of functional ingredients has been suggested to be a complementary tool for the prevention and management of liver disease. In this light, processed onion can be considered as a source of multiple bioactive compounds with hepatoprotective properties. The liver fingerprint of male Wistar rats (n = 24) fed with three experimental diets (control (C), high-cholesterol (HC), and high-cholesterol enriched with onion (HCO) diets) was obtained through a non-targeted, multiplatform metabolomics approach to produce broad metabolite coverage. LC-MS, CE-MS and GC-MS results were subjected to univariate and multivariate analyses, providing a list of significant metabolites. All data were merged in order to figure out the most relevant metabolites that were modified by the onion ingredient. Several relevant metabolic changes and related metabolic pathways were found to be impacted by both HC and HCO diet. The model highlighted several metabolites (such as hydroxybutyryl carnitine and palmitoyl carnitine) modified by the HCO diet. These findings could suggest potential impairments in the energy−lipid metabolism, perturbations in the tricarboxylic acid cycle (TCA) cycle and β-oxidation modulated by the onion supplementation in the core of hepatic dysfunction. Metabolomics shows to be a valuable tool to evaluate the effects of complementary dietetic approaches directed to hepatic damage amelioration or non-alcoholic fatty liver disease (NAFLD) prevention.

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“…The blood glucose can be metabolized into small molecule metabolites and then enter the TCA‐cycle, which is directly coupled to myocardial oxygen consumption. This cycle plays a key role in cell metabolism and the levels of the involved metabolites can also be affected by other physiological factors (HbA1c) . Recent study demonstrates that residents living in the pollution‐affected area always be with higher levels of urine metabolite profiles, incorporating phenylalanine metabolism and alanine, aspartate and glutamate metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…This cycle plays a key role in cell metabolism and the levels of the involved metabolites can also be affected by other physiological factors (HbA1c). 25 Recent study demonstrates that residents living in the pollution-affected area always be with higher levels of urine metabolite profiles, incorporating phenylalanine metabolism and alanine, aspartate and glutamate metabolism. Those metabolites are linked to increased oxidative stress, including oxidative and nitrative DNA damage, and lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolites mediate the effect of HbA1c on incident cardiovascular disease

Dong

Fan

et al. 2019

Clinical Cardiology

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Background We aim to discover whether HbA1c affects incident cardiovascular disease (CVD) through regulating endogenous metabolites. Methods and Results Totally, 2019 plasma samples were analyzed by liquid chromatography‐quadrupole time‐of‐flight mass spectrometry. Logistic regression and linear regression were used to screen metabolites which were associated with both CVD and HbA1c. The VanderWeele's mediation approach was performed to assess the direct effect and indirect effect (IE) in the counterfactual model. Forty‐eight metabolites showed an association with both HbA1c and CVD risk. Forty‐four of the 48 metabolites worked as mediators mediated in HbA1c's effect on CVD (odds ratio [OR]IE from 0.997 to 6.098, false discovery rate q < 0.05, mediated proportion from 0.4% to 85.4%). Pathway enrichment analysis indicated that different metabolic pathway showed significant IE (butanoate metabolism ORIE = 1.058, mediated proportion = 16.0%; alanine, aspartate and glutamate metabolism ORIE = 1.082, mediated proportion = 21.8%; TCA (citric acid) cycle metabolism ORIE = 1.048, mediated proportion = 13.8%; phenylalanine metabolism ORIE = 1.067, mediated proportion = 18.4%; glycerophospholipid metabolism ORIE = 3.007, mediated proportion = 82.2%; all the P < .01). Conclusions Our findings suggest that metabolites mediate the effect of HbA1c on incident CVD and provide a new study sight into pathogenesis of CVD.

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Method based on GC–MS to study the influence of tricarboxylic acid cycle metabolites on cardiovascular risk factors

Cited by 29 publications

References 28 publications

Metabolic profiling by gas chromatography-mass spectrometry of energy metabolism in high-fat diet-fed obese mice

Metabolic profiling by gas chromatography-mass spectrometry of energy metabolism in high-fat diet-fed obese mice

Metabolomic Fingerprinting in the Comprehensive Study of Liver Changes Associated with Onion Supplementation in Hypercholesterolemic Wistar Rats

Plasma metabolites mediate the effect of HbA1c on incident cardiovascular disease

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